Quantifying the ki-67 heterogeneity profile in prostate cancer.

BackgroundKi-67 is a robust predictive/prognostic marker in prostate cancer; however, tumor heterogeneity in prostate biopsy samples is not well studied.MethodsUsing an MRI/US fusion device, biopsy cores were obtained systematically and by targeting when indicated by MRI. Prostate cores containing cancer from 77 consecutive men were analyzed. The highest Ki-67 was used to determine interprostatic variation. Ki-67 range (highest minus lowest) was used to determine intraprostatic and intralesion variation. Apparent diffusion coefficient (ADC) values were evaluated in relation to Ki-67.ResultsInterprostatic Ki-67 mean ± standard deviation (SD) values for NCCN low (L), intermediate (I), and high (H) risk patients were 5.1 ± 3.8%, 7.4 ± 6.8%, and 12.0 ± 12.4% (ANOVA P = 0.013). Intraprostatic mean ± SD Ki-67 ranges in L, I, and H risk patients were 2.6 ± 3.6%, 5.3 ± 6.8%, and 10.9 ± 12.3% (ANOVA P = 0.027). Intralesion mean ± SD Ki-67 ranges in L, I, and H risk patients were 1.1 ± 0.9%, 5.2 ± 7.9%, and 8.1 ± 10.8% (ANOVA P = 0.22). ADC values at Ki-67 > and <7.1% were 860 ± 203 and 1036 ± 217, respectively (P = 0.0029).ConclusionsHigh risk patients have significantly higher inter- and intraprostatic Ki-67 heterogeneity. This needs to be considered when utilizing Ki-67 clinically

The Complexity of Local Proof Search in Linear Logic (Extended Abstract)

AbstractProof search in linear logic is known to be difficult: the provability of propositional linear logic formulas is undecidable. Even without the modalities, multiplicative-additive fragment of propositional linear logic, mall, is known to be PSPACE-complete, and the pure multiplicative fragment, mll, is known to be np-complete. However, this still leaves open the possibility that there might be proof search heuristics (perhaps involving randomization) that often lead to a proof if there is one, or always lead to something close to a proof. One approach to these problems is to study strategies for proof games. A class of linear logic proof games is developed, each with a numeric score that depends on the number of certain preferred axioms used in a complete or partial proof tree. Using recent techniques for proving lower bounds on optimization problems, the complexity of these games is analyzed for the fragment mll extended with additive constants and for the fragment MALL. It is shown that no efficient heuristics exist unless there is an unexpected collapse in the complexity hierarchy

Modeling Peste des Petits Ruminants (PPR) Disease Propagation and Control Strategies Using Memoryless State Transitions

Peste des Petits Ruminants (PPR) is an infectious disease affecting goats and sheep. PPR has a mortality rate of 80% and a morbidity rate of 100% in naïve herds. This disease is currently of concern to Afghani goat and sheep herders as conditions in Afghanistan are conducive to the disease becoming an epidemic. PPR is similar to Rinderpest, but is not as well studied. There is a lack of empirical data on how the disease spreads or effective large-scale mitigation strategies. We developed a herd-level, event-driven model of PPR, using memoryless state transitions, to study how the virus propagates through a herd, and to identify effective control strategies for disparate herd configurations and environments. This model allows us to perform Sensitivity Analyses (SA) on environmental and disease parameters for which we do not have empirical data and to simulate the effectiveness of various control strategies. We find that reducing the amount of time from the identification of PPR in a herd to the vaccination of the herd will radically reduce the number of deaths that result from PPR. The goal of this model is to give policy makers a tool to develop effective containment strategies for managing outbreaks of PPR

Funding for mental health research: the gap remains

Objectives: To examine the levels and growth rates of absolute funding to mental health research from 2001 to 2010, compared with other National Health Priority Areas (NHPAs), and the relative rate of mental health funding compared with other NHPAs, by taking disease burden into account. The quality of Australian research in mental health was also examined using objective indicators of research strength. Design and setting: Retrospective analysis of levels of funding overall and as a function of mental health domains using data from the National Health and Medical Research Council, with and without adjustment for burden of disease. A keyword analysis was used to assess the success rate of mental health project grant applications. Objective indicators of the quality of Australian mental health research were sought from citation indicators. Main outcome measures: Funding for mental health research relative to disease burden; funding according to disease category; project grant success rates. Results: Using actual and adjusted figures, mental health research received a lower proportion of health funding than other NHPAs, including cancer, diabetes and cardiovascular disease. Research projects into substance misuse and autism were proportionately better funded than those in anxiety, depression or schizophrenia. A significant proportion of mental health research funding was awarded to research into ageing. Citation data indicated that mental health research in Australia performed better than research in neuroscience, clinical medicine, microbiology, and pharmacology and toxicology, and at a comparable level to immunology research, despite poor levels of funding. Conclusions: Low levels of funding for mental health research appear to be largely attributable to low capacity. Mental health research in Australia is of high quality, and efforts are needed to build capacity

Association between bilirubin and cardiovascular disease risk factors: using Mendelian randomization to assess causal inference

Background: Elevated serum bilirubin has been associated with reduced risk of cardiovascular disease (CVD). However, serum bilirubin is also related with several potential confounders related to CVD, such as obesity. Mendelian randomization has been proposed as a method to address challenges to validity from confounding and reverse causality. It utilizes genotype to estimate causal relationships between a gene product and physiological outcomes. In this report, we demonstrate its use in assessing direct causal relations between serum bilirubin levels and CVD risk factors, including obesity, cholesterol, measures of vascular function and blood pressure. Methods: Study subjects included 868 asymptomatic individuals. Study subjects were genotyped at the UGT1A1*28 locus, which is strongly associated with bilirubin levels. Results: Serum bilirubin levels were inversely associated with levels of several cardiovascular disease risk factors, including body mass index (p = 0.003), LDL (p = 0.0005) and total cholesterol (p = 0.0002). In contrast, UGT1A1*28 genotype, a known cause of elevated bilirubin levels, was not significantly associated with any of these traditional CVD risk factors. We did observe an association between genotype and brachial artery diameter (p = 0.003) and cold pressor reactivity (p = 0.01). Conclusions: Our findings imply that the observed association of serum bilirubin levels with body mass index and cholesterol are likely due to confounding and suggest that previously established CVD benefits of increased bilirubin may in part be mediated by the early regulation of vascular structure and reactivity

Enhancing Self-Consistency and Performance of Pre-Trained Language Models through Natural Language Inference

While large pre-trained language models are powerful, their predictions often lack logical consistency across test inputs. For example, a state-of-the-art Macaw question-answering (QA) model answers 'Yes' to 'Is a sparrow a bird?' and 'Does a bird have feet?' but answers 'No' to 'Does a sparrow have feet?'. To address this failure mode, we propose a framework, Consistency Correction through Relation Detection, or ConCoRD, for boosting the consistency and accuracy of pre-trained NLP models using pre-trained natural language inference (NLI) models without fine-tuning or re-training. Given a batch of test inputs, ConCoRD samples several candidate outputs for each input and instantiates a factor graph that accounts for both the model's belief about the likelihood of each answer choice in isolation and the NLI model's beliefs about pair-wise answer choice compatibility. We show that a weighted MaxSAT solver can efficiently compute high-quality answer choices under this factor graph, improving over the raw model's predictions. Our experiments demonstrate that ConCoRD consistently boosts accuracy and consistency of off-the-shelf closed-book QA and VQA models using off-the-shelf NLI models, notably increasing accuracy of LXMERT on ConVQA by 5% absolute. See https://ericmitchell.ai/emnlp-2022-concord/ for code and data.Comment: 16 pages. EMNLP 2022 Camera Ready. See https://ericmitchell.ai/emnlp-2022-concord/ for code and dat

The Effect of CardioWaves Interval Training on Resting Blood Pressure, Resting Heart Rate, and Mind-Body Wellness

International Journal of Exercise Science 9(1): 89-100, 2016. An experimental study to examine the effects of CardioWaves interval training (CWIT) and continuous training (CT) on resting blood pressure, resting heart rate, and mind-body wellness. Fifty-two normotensive (blood pressure \u3c120/80 mmHg), pre-hypertensive (120–139/80–89 mmHg), and hypertensive (\u3e140/90 mmHg) participants were randomly assigned and equally divided between the CWIT and CT groups. Both groups participated in the assigned exercise protocol 30 minutes per day, four days per week for eight weeks. Resting blood pressure, resting heart rate, and mind-body wellness were measured pre- and post-intervention. A total of 47 participants (15 females and 32 males) were included in the analysis. The CWIT group had a non-significant trend of reduced systolic blood pressure (SBP) and increased diastolic blood pressure (DBP) while the CT group had a statistically significant decrease in awake SBP (p = 0.01) and total SBP (p = 0.01) and a non-significant decrease in DBP. With both groups combined, the female participants had a statistically significant decrease in awake SBP (p = 0.002), asleep SBP (p = 0.01), total SBP (p = 0.003), awake DBP (p = 0.02), and total DBP (p = 0.05). The male participants had an increase in SBP and DBP with total DBP showing a statistically significant increase (p = 0.05). Neither group had a consistent change in resting heart rate. Both groups showed improved mind-body wellness. CWIT and CT reduced resting blood pressure, with CT having a greater effect. Resting heart rate did not change in either group. Additionally, both CWIT and CT improved mind-body wellness

Missouri Representative Farms Financial Projections

This document presents an estimate of financial risk on individual Missouri representative farms in future years.This material is based upon work supported by Cooperative States Research Education and Extension Service, U.S. Department of Agriculture, under Agreement No. 00-34228-8988 and Missouri Department of Agriculture proposal #00112091